Remodeling of tissue-engineered bone structures in vivo.

Implant design for bone regeneration is expected to be optimized when implant structures resemble the anatomical situation of the defect site. We tested the validity of this hypothesis by exploring the feasibility of generating different in vitro engineered bone-like structures originating from porous silk fibroin scaffolds decorated with RGD sequences (SF-RGD), seeded with human mesenchymal stem cells (hMSC). Scaffolds with small (106 – 212 μm), medium (212 – 300 μm) and large pore diameter ranges (300 – 425 μm) were seeded with hMSC and subsequently differentiated in vitro into bone-like tissue resembling initial scaffold geometries and featuring bone-like structures. Eight weeks after implantation into calvarial defects in mice, the in vitro engineered bone-like tissues had remodeled into bone featuring different proportions of woven/lamellar bone bridging the defects. Regardless of pore diameter all implants integrated well, vascularization was advanced and, bone marrow ingrowth had started. Ultimately, in this defect model, the geometry of the in vitro generated tissue-engineered bone structure, trabecular- or plate-like, had no significant impact on the healing of the defect, owing to an efficient remodeling of its structure after implantation.

当植入物结构类似于缺损部位的解剖情况时，骨再生的植入物设计有望得到优化。我们通过探索利用带有RGD序列的多孔丝素蛋白支架（SF - RGD），接种人间充质干细胞（hMSC）来生成不同的体外工程化骨样结构的可行性，检验了这一假设的有效性。将具有小（106 - 212μm）、中（212 - 300μm）和大（300 - 425μm）孔径范围的支架接种hMSC，随后在体外分化为类似于初始支架几何形状且具有骨样结构的骨样组织。在植入小鼠颅骨缺损处8周后，体外工程化骨样组织已重塑为具有不同比例的编织骨/板层骨来桥接缺损的骨组织。无论孔径大小，所有植入物均整合良好，血管化进展良好，且骨髓已开始向内生长。最终，在该缺损模型中，由于植入后其结构的有效重塑，体外生成的组织工程化骨结构（小梁状或板状）的几何形状对缺损的愈合没有显著影响。